RESUMO
Patients with atopic dermatitis (AD) are frequently colonized with Staphylococcus aureus, with one-third of isolates producing alpha-toxin. Moreover, S. aureus colonization is positively correlated with the severity of eczema. Interleukin-17A (IL-17A) has gained attention in diseases associated with chronic skin infections. The aim of this study was to investigate the effects of sublytic alpha-toxin concentrations on IL-17A production. Sublytic alpha-toxin concentrations strongly induced IL-17A in peripheral blood mononuclear cells (PBMCs), isolated CD4(+) T cells, polarized Th17 cells, and Th17 clones from reactive atopy patch test lesions and blood from AD patients. Alpha-toxin induced IL-17A directly in T cells. The effect of alpha-toxin was further amplified by upregulation of IL-1 in monocytes. In conclusion, higher levels of IL-17A secretion induced by alpha-toxin in the skin partially explain how colonization with S. aureus can contribute to chronic skin inflammation.
Assuntos
Toxinas Bacterianas/imunologia , Dermatite Atópica/microbiologia , Proteínas Hemolisinas/imunologia , Interleucina-17/biossíntese , Infecções Cutâneas Estafilocócicas/complicações , Infecções Cutâneas Estafilocócicas/microbiologia , Toxinas Bacterianas/metabolismo , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Separação Celular , Células Cultivadas , Dermatite Atópica/imunologia , Dermatite Atópica/metabolismo , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Proteínas Hemolisinas/metabolismo , Humanos , Interleucina-1/biossíntese , Interleucina-1/imunologia , Interleucina-17/imunologia , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Infecções Cutâneas Estafilocócicas/imunologia , Staphylococcus aureus/imunologia , Staphylococcus aureus/metabolismo , Células Th17/imunologia , Células Th17/metabolismo , Regulação para CimaRESUMO
BACKGROUND: Patients with atopic dermatitis (AD) and psoriasis are frequently colonized with Staphylococcus aureus that produces staphylococcal enterotoxin B (SEB) and α-toxin. In patients with AD, S aureus colonization is positively correlated with the severity of their eczema. Moreover, IL-22-producing cells have been shown to accumulate in AD skin and to correlate with disease severity. OBJECTIVE: To assess IL-22 production in response to SEB and sublytic α-toxin stimulation in patients with AD and psoriasis compared with healthy controls. METHODS: IL-22 induction was investigated in PBMCs, T cells, and autologous cocultures of keratinocytes and T cells on SEB and α-toxin stimulation in a time-dependent and dose-dependent manner at the mRNA and protein (ELISA and flow cytometry) level. Anti-IL-1 receptor or anti-IL-6 antibodies were used in blocking experiments. RESULTS: Staphylococcal enterotoxin B and sublytic α-toxin concentrations induced IL-22 production in PBMCs and isolated CD4(+) T cells. IL-22 secretion was enhanced by α-toxin stimulation in autologous cocultures of keratinocytes and T cells. In T cells and PBMCs from patients with AD, IL-22 secretion was significantly enhanced on α-toxin stimulation compared with patients with psoriasis and healthy controls. CONCLUSION: Increased IL-22 secretion induced by staphylococcal exotoxins in the skin partially explains how skin colonization and infection with S aureus can contribute to chronic skin inflammation in AD.
